1. Field of the Invention
The invention is in the field of mass spectrometry, and in particular detection electronics for time-of-flight mass spectrometry.
2. Related Art
Time-of-flight mass spectrometry (TOFMS) is based upon the principle that ions of different mass-to-charge ratios that are accelerated to the same kinetic energy travel at different velocities. As such, ions of a first mass-to-charge ratio will take a different amount of time to travel a fixed distance than ions of a second mass-to-charge ratio. By detecting the arrival times of ions at the end of the fixed distance, a mass spectrum can be generated.
TOFMS is typically operated in a so-called cyclic mode, in which successive bunches of ions are accelerated to a kinetic energy, separated in flight according to their mass-to-charge ratios, and then detected. In each cycle a complete mass spectrum can be recorded. However, typically, the results of many cycles are combined to generate a mass spectrum with improved signal to noise ratios.
One of the primary challenges in TOFMS is to maximize the dynamic range of detectable ion signals. The dynamic range is limited by the detector and subsequent signal processing electronics. The challenge is to simultaneously determine the number of ions detected and their arrival times. In some situations it is desirable to determine arrival times to within nanosecond or sub-nanosecond time scales. Thus, the detector and signal processing electronics must be able to quantitatively record events in very rapid succession.
Signal processing electronics for use in TOFMS systems typically fall into two classifications, transient recorders and time-to-digital converters (TDCs). In all of these systems detected signals are divided into separate “time bins” responsive to when they were detected. In the art, the term “time bin” can refer to either a time interval or a field within a data buffer used to store data regarding events that occurred during that time interval. Each time bin is associated with a particular time relative to a trigger signal.
Transient recorders include analog-to-digital converters (ADCs) configured to convert an electronic signal received from a detector anode to a digital value. Transient recorders typically have a dynamic range of 8, 12 or 16 bits in signal intensity. A separate analog-to-digital conversion occurs for each time bin of a transient recorder. There can be many thousands of time bins and thus a significant amount of data to generate process and store. The time required to perform each analog-to-digital conversion and transfer the result to an electronic storage location limits the maximum time resolution and duty cycle of transient recorders.
Because of the limitations of transient recorders, most high resolution time-of-flight mass spectrometry is performed using TDCs. TDCs employ an ion counting approach that eliminates the need for multi-bit analog-to-digital conversion and for rapid storage of multi-bit data. TDCs typically have advantages over transient recorders in terms of cost and detector compatibility.
In the ion counting approach used by TDCs, if an ion is detected in a specific time bin then a “1” is placed in that time bin, otherwise a “0” is placed in that time bin. Thus, TDCs have a dynamic range of one bit. The bit is turned on (switched from zero to one) by comparing the received electronic signal with a reference voltage at the time represented by each time bin. This comparison is typically made using a discriminator. The impact of a single ion is, thus, converted to a first binary value, e.g., 1 and the lack of impact is represented as a second binary value (e.g., 0). A mass spectrum is generated by summing the 1-bit TDC data over many measurement (e.g., data acquisition) cycles. Typically, this summation takes place within a memory included within the TDC. A prior art TDC is capable of detecting at most one type of event at a time. Thus, by appropriate selection of discriminator logic, a prior art TDC can be configured to detect a rising edge of a pulse or, alternatively, a falling edge of a pulse, but not both at the same time.
There are, however, several disadvantages to TDCs. First, the output of the TDC will be a “1” regardless of whether one, two or more ions are received by the detector within the same time bin. This can result in a bias against stronger signals and suppression of some peaks in the final summed mass spectrum. Second, TDCs are subject to a “dead-time.” Dead-time is a time immediately following the detection of an event (in this case the arrival of an ion) during which no further events can be distinguished. Thus, if a subsequent ion arrives during the dead-time caused by the arrival of a first ion, the subsequent ion will not be detected as a separate event. In addition, the arrival of the subsequent ion can extend the duration of the dead-time. Thus, there is a bias in which earlier ions may be digitized by the TDC, while later ones may not.
The above problems with TDCs result in peak distortion in resulting mass spectra. Observed peaks can be reduced in absolute height, since some ions are not counted. When this occurs, the resulting mass spectrum will include unrepresentative peak ratios. Observed peaks can also be shifted in time because of the bias toward the first ions to be received. When this occurs, the peak may be assigned an inaccurate mass-to-charge ratio. In TOFMS this is referred to as a mass shift. Both of the above effects are undesirable.
One solution to peak distortion caused by dead-time is to keep the ion detection rates so low that the peak distortions become negligible. However, if the ion detection rates are too low, the sensitivity and dynamic range of the analysis are adversely affected. Another solution is to apply statistical corrections to the summed mass spectrum in order to minimize the impact of dead-time. However, these corrections are typically only appropriate over a relatively limited range.
Other approaches to solving peak distortion problems caused by dead-time have included using multiple detection anodes, each with a separate TDC, or the use of a transient recorder in parallel with a TDC.
All of these approaches have disadvantages associated with cost, dynamic range, cross-talk, data processing, and the like. There is, therefore, a need for improved methods of ion detection using TDCs.